Inhibition of release of tumor necrosis factor-α from human vascular tissue and smooth muscle cells by glucocorticoids

Walter H. Newman, Li Ming Zhang, Sandra K. Leeper-Woodford, Isaam J. Shaker, Stefan K. Erceg, Manuel R. Castresana

Research output: Contribution to journalArticle

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Abstract

Objectives: Based on our previous study that bacterial lipopolysaccharide stimulates release of tumor necrosis factor (TNF)-α from human vascular tissue and smooth muscle cells, we tested the hypothesis that release of TNF could be inhibited by pretreatment with glucocorticoids. Design: Prospective, repeated-measures analysis of concentration-response relationships. Setting: Academic anesthesiology research laboratory. Subjects: Segments of internal mammary artery and saphenous vein were obtained during coronary artery bypass surgery. Interventions: None. Measurements and Main Results: Confluent human smooth muscle cells, cultured from saphenous vein and internal mammary artery, were exposed to 20 μg/mL of bacterial lipopolysaccharide following pretreatment for 18 hrs with either 0.1, 1.0, or 10.0 μM of dexamethesone. At 1, 3, 6, 18, and 24 hrs, the culture medium was removed and analyzed for biologically active TNF-α using the L929 cell cytotoxicity assay. Smooth muscle cells exposed to bacterial lipopolysaccharide but not treated with dexamethasone served as controls. In control internal mammary cells, bacterial lipopolysaccharide stimulated TNF- α release in a time-dependent manner to a peak of 36 ± 2.3 U/mg of cell protein at 6 hrs, compared with 0.7 ± 0.3 U/mg of cell protein in cells not exposed to lipopolysaccharide. Dexamethasone inhibited bacterial lipopolysaccharide-stimulated release at all time points in a concentration- dependent manner. For instance, at 6 hrs, TNF-α was 12 ± 2.2, 6.9 ± 1.7, and 2.3 ± 0.9 U/mg of cell protein for cells pretreated with 0.1, 1.0, and 10.0 μM of dexamethasone, respectively (p < .05 vs. control). In separate experiments, segments of internal mammary artery and saphenous vein were obtained from five patients who received 1 g of methyl-prednisolone intravenously during induction of anesthesia, and from seven patients who did not receive methylprednisolone. Bacterial lipopolysaccharide induced release of TNF-α from vascular tissues of untreated patients in a time-dependent manner (e.g., 733 ± 44 U/g of tissue at 6 hrs in saphenous vein). In contrast, in patients treated with methylprednisolone, bacterial lipopolysaccharide did not stimulate release from vascular tissues incubated for up to 24 hrs. Conclusions: These results indicate that human vascular tissue, particularly the smooth muscle cell, may be a source of TNF-α and that glucocorticoids inhibit release stimulated by bacterial lipopolysaccharide.

Original languageEnglish (US)
Pages (from-to)519-522
Number of pages4
JournalCritical care medicine
Volume25
Issue number3
DOIs
StatePublished - Mar 1 1997
Externally publishedYes

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Vascular Smooth Muscle
Glucocorticoids
Smooth Muscle Myocytes
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Saphenous Vein
Mammary Arteries
Dexamethasone
Blood Vessels
Methylprednisolone
human TNF protein
Proteins
Anesthesiology
Prednisolone
Coronary Artery Bypass
Culture Media
Breast
Anesthesia
Research

Keywords

  • TNF
  • blood vessels
  • glucocorticoids
  • smooth muscle cells

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Inhibition of release of tumor necrosis factor-α from human vascular tissue and smooth muscle cells by glucocorticoids. / Newman, Walter H.; Zhang, Li Ming; Leeper-Woodford, Sandra K.; Shaker, Isaam J.; Erceg, Stefan K.; Castresana, Manuel R.

In: Critical care medicine, Vol. 25, No. 3, 01.03.1997, p. 519-522.

Research output: Contribution to journalArticle

Newman, Walter H. ; Zhang, Li Ming ; Leeper-Woodford, Sandra K. ; Shaker, Isaam J. ; Erceg, Stefan K. ; Castresana, Manuel R. / Inhibition of release of tumor necrosis factor-α from human vascular tissue and smooth muscle cells by glucocorticoids. In: Critical care medicine. 1997 ; Vol. 25, No. 3. pp. 519-522.
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